The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non-small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. ...Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio HR, 0.68; 95% CI, 0.53 to 0.87;
= .00251) and progression-free survival (PFS blinded independent central review; RECIST v1.1; stratified HR, 0.52; 95% CI, 0.42 to 0.65;
< .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.
Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method.
Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months all patients; 61.6 months censored patients), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5
29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9
5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS.
These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.
Abstract Modern wind turbines in standstill or idling could experience vortex induced vibrations (VIV); the origin of these vibrations is either shedding from the wind turbine blade referred to as ...blade VIV or shedding from tower termed as tower (or turbine) VIV. When the whole structure of the wind turbine is considered and the blades are pitched out, the dominant 1st order mode for blade deformation in edgewise direction leads to negligible motion of the tower top, while when the whole turbine vibrates with first tower mode, blades also undergo significant periodic translations and deformations. In this study, forced motion is used to study the impact of aerodynamic damping due to rotor moving with 1st tower mode. In the literature no comprehensive work is available to characterize the impact of blades aerodynamics in the turbine mode either using systematic tests or high-fidelity computational fluid dynamics (CFD). In this article high-fidelity numerical simulations are performed to compute the power injections from the rotor blades when the turbine moves in 1st tower mode. Depending on the inflow angle and the azimuthal position, blades can inject significant power. Thus, the estimated damping from tower-only empirical models could severely underestimate the total aerodynamic power if the power injection from the rotor is neglected.
Background
The COVID-19 global health crisis has led to an exponential surge in published scientific literature. In an attempt to tackle the pandemic, extremely large COVID-19–related corpora are ...being created, sometimes with inaccurate information, which is no longer at scale of human analyses.
Objective
In the context of searching for scientific evidence in the deluge of COVID-19–related literature, we present an information retrieval methodology for effective identification of relevant sources to answer biomedical queries posed using natural language.
Methods
Our multistage retrieval methodology combines probabilistic weighting models and reranking algorithms based on deep neural architectures to boost the ranking of relevant documents. Similarity of COVID-19 queries is compared to documents, and a series of postprocessing methods is applied to the initial ranking list to improve the match between the query and the biomedical information source and boost the position of relevant documents.
Results
The methodology was evaluated in the context of the TREC-COVID challenge, achieving competitive results with the top-ranking teams participating in the competition. Particularly, the combination of bag-of-words and deep neural language models significantly outperformed an Okapi Best Match 25–based baseline, retrieving on average, 83% of relevant documents in the top 20.
Conclusions
These results indicate that multistage retrieval supported by deep learning could enhance identification of literature for COVID-19–related questions posed using natural language.
Abstract This manuscript presents findings from a preregistered mixed-method study involving 67,762 ecological momentary assessments and behavioral smartphone observations from 1,315 adults. The ...study investigates (a) momentary associations between mindless scrolling, goal conflict, and guilt over smartphone use, and (b) whether guilt experiences during the day culminate into lower well-being. Results indicate that individuals experienced more guilt over their smartphone use when they had mindlessly scrolled for a longer period and that experienced goal conflict partially mediated this relationship. Daily analyses revealed that mindless scrolling was also associated with small negative changes in well-being, and this relationship was partially mediated by guilt experienced over the same day. Individuals with less self-control were more prone to experiencing goal conflict after mindlessly scrolling. These findings indicate that although mindless scrolling may seem a relatively harmless media behavior, it may have both momentary and downstream negative implications for well-being.
Dam safety assessment is typically made by comparison between the outcome of some predictive model and measured monitoring data. This is done separately for each response variable, and the results ...are later interpreted before decision making. In this work, three approaches based on machine learning classifiers are evaluated for the joint analysis of a set of monitoring variables: multi-class, two-class and one-class classification. Support vector machines are applied to all prediction tasks, and random forest is also used for multi-class and two-class. The results show high accuracy for multi-class classification, although the approach has limitations for practical use. The performance in two-class classification is strongly dependent on the features of the anomalies to detect and their similarity to those used for model fitting. The one-class classification model based on support vector machines showed high prediction accuracy, while avoiding the need for correctly selecting and modelling the potential anomalies. A criterion for anomaly detection based on model predictions is defined, which results in a decrease in the misclassification rate. The possibilities and limitations of all three approaches for practical use are discussed.
Los debates electorales representan una cita ineludible para candidatos y electorado en las sociedades modernas. En España se han celebrado un total de 5 encuentros entre los líderes políticos ...durante el año 2019. Hasta la fecha, la política medioambiental ha sido la gran olvidada en este tipo de eventos. Sin embargo, la creciente preocupación a nivel social, mediático y político permite augurar su incorporación a la campaña. Nuestra investigación parte del análisis de contenido para detectar la presencia de discursos medioambientales durante los debates, y aplica la teoría funcional y el framing para determinar el contenido, la forma y el encuadre utilizado. Los resultados demuestran una progresiva incorporación de la emergencia climática a los debates electorales, descrita en términos de enfrentamiento ideológico y en clave económica.
Electoral debates are unmissable events for candidates and voters in modern societies. In 2019, political leaders held a total of 5 debates in Spain. To date, environmental policy has been largely forgotten in this type of event. However, the growing concern at the social, media and political level means that there is a likelihood of them being included in the campaign. This study starts with a content analysis to identify the presence of environmental discourses in electoral debates and applies Functional Theory and Framing Theory to determine the content, form and framing used. The results showed a progressive inclusion of the climate emergency into electoral debates, described in terms of ideological confrontation and in economic terms.
The possibility of emergence of praziquantel-resistant Schistosoma parasites and the lack of other effective drugs demand the discovery of new schistosomicidal agents. In this context the study of ...compounds that target histone-modifying enzymes is extremely promising. Our aim was to investigate the effect of inhibition of EZH2, a histone methyltransferase that is involved in chromatin remodeling processes and gene expression control; we tested different developmental forms of Schistosoma mansoni using GKS343, a selective inhibitor of EZH2 in human cells.
Adult male and female worms and schistosomula were treated with different concentrations of GSK343 for up to two days in vitro. Western blotting showed a decrease in the H3K27me3 histone mark in all three developmental forms. Motility, mortality, pairing and egg laying were employed as schistosomicidal parameters for adult worms. Schistosomula viability was evaluated with propidium iodide staining and ATP quantification. Adult worms showed decreased motility when exposed to GSK343. Also, an approximate 40% reduction of egg laying by GSK343-treated females was observed when compared with controls (0.1% DMSO). Scanning electron microscopy showed the formation of bulges and bubbles throughout the dorsal region of GSK343-treated adult worms. In schistosomula the body was extremely contracted with the presence of numerous folds, and growth was markedly slowed. RNA-seq was applied to identify the metabolic pathways affected by GSK343 sublethal doses. GSK343-treated adult worms showed significantly altered expression of genes related to transmembrane transport, cellular homeostasis and egg development. In females, genes related to DNA replication and noncoding RNA metabolism processes were downregulated. Schistosomula showed altered expression of genes related to cell adhesion and membrane synthesis pathways.
The results indicated that GSK343 presents in vitro activities against S. mansoni, and the characterization of EZH2 as a new potential molecular target establishes EZH2 inhibitors as part of a promising new group of compounds that could be used for the development of schistosomicidal agents.
The discrete element method (DEM) is well suited for calculating the behaviour of bulk materials. However, its application is limited because of the cumbersome calibration process required. Trial and ...error calibration can be useful for the computation of single outputs, but is unfeasible when the aim is reproducing more complex phenomena with high accuracy. This paper describes an iterative procedure based on machine learning to automatically calibrate the parameters of DEM models for reproducing the behaviour of bulk materials. The performance of the methodology is assessed by its application to the calibration of a DEM model to compute the stress–strain evolution of a cohesive material under uniaxial compression. In this case, a random forest model is used in conjunction with the iterative calibration algorithm proposed. The results of this study show that the algorithm is accurate and flexible for the calibration of material parameters.
The scientific consensus on the existence, the human origin, the seriousness of the consequences and the urgency of adopting immediate solutions to climate change is growing, as successive reports by ...the Intergovernmental Panel on Climate Change have shown. The alteration of global climate patterns experienced in recent years confirms the worst prediction models, and yet there are still voices that question these facts. This study proposes to examine the interpretative frameworks underpinning public discussion of climate denialism on the online video platform YouTube. To this end, it presents an analysis of the 50 most popular videos under the label of climate denialism in Spanish, paying attention to the key issues and figures on which the denialist ideology is articulated and the attitude of support, neutrality or rejection on the part of those responsible for the content. The results obtained show the generalized rejection of the denialist discourse among Spanish-speaking content creators, who resort to experienced sources and contrasted resources to refute these arguments, as well as the politicization of scientific knowledge in terms of debate, uncertainty, mistrust and lack of commitment to deal with the consequences.
is a flatworm that causes schistosomiasis, a neglected tropical disease.
RNA-Seq analyses has been previously reported in the literature on females and males obtained during sexual maturation from 14 ...to 28 days post-infection in mouse, resulting in the identification of protein-coding genes and pathways, whose expression levels were related to sexual development. However, this work did not include an analysis of long non-coding RNAs (lncRNAs). Here, we applied a pipeline to identify and annotate lncRNAs in 66
RNA-Seq publicly available libraries, from different life-cycle stages. We also performed co-expression analyses to find stage-specific lncRNAs possibly related to sexual maturation. We identified 12,291
expressed lncRNAs. Sequence similarity search and synteny conservation indicated that some 14% of
intergenic lncRNAs have synteny conservation with
intergenic lncRNAs. Co-expression analyses showed that lncRNAs and protein-coding genes in
males and females have a dynamic co-expression throughout sexual maturation, showing differential expression between the sexes; the protein-coding genes were related to the nervous system development, lipid and drug metabolism, and overall parasite survival. Co-expression pattern suggests that lncRNAs possibly regulate these processes or are regulated by the same activation program as that of protein-coding genes.
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